Defective retrovirus insertion activates c-Ha-ras protooncogene in an MNU-induced rat mammary carcinoma

Biochem Biophys Res Commun. 1998 Jul 30;248(3):835-40. doi: 10.1006/bbrc.1998.9059.


Endogenous retrovirus sequences are present in the genome of a wide variety of animal species. The activation of the proto-oncogenes of the ras family, particularly c-Ha-ras, by either point mutation or overexpression, has been shown to be associated with a vast number, of different cancers. here we report that the insertion of a defective retrovirus in the -1 intron of rat c-Ha-ras is responsible for the activation of the gene by over 10-fold overexpression in an MNU-induced rat mammary cancer. A portion of the 3' end of the retroviral sequence is expressed as a part of the c-Ha-ras transcript in the carcinoma tissue, indicating the direct involvement of this element in the transcription of the c-Ha-ras gene. The c-Ha-ras structural gene transcribed by the promoter of the defective retroviral element can neoplastically transform the NIH 3T3 cell line upon transfection.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Cell Transformation, Neoplastic*
  • Defective Viruses / genetics
  • Defective Viruses / physiology*
  • Exons
  • Female
  • Genes, env
  • Genes, ras*
  • Introns
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / genetics*
  • Mammary Neoplasms, Experimental / metabolism*
  • Methylnitrosourea
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins p21(ras) / biosynthesis*
  • Rats
  • Recombinant Proteins / biosynthesis
  • Repetitive Sequences, Nucleic Acid
  • Retroviridae / genetics
  • Retroviridae / physiology*
  • Transfection


  • Recombinant Proteins
  • Methylnitrosourea
  • Proto-Oncogene Proteins p21(ras)